| First Author | Nakajima A | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 30 | Pages | 12448-52 |
| PubMed ID | 19617565 | Mgi Jnum | J:150948 |
| Mgi Id | MGI:3852578 | Doi | 10.1073/pnas.0905702106 |
| Citation | Nakajima A, et al. (2009) Cell type-dependent proapoptotic role of Bcl2L12 revealed by a mutation concomitant with the disruption of the juxtaposed Irf3 gene. Proc Natl Acad Sci U S A 106(30):12448-52 |
| abstractText | The generation of mice lacking the expression of the IRF3 transcription factor (Irf3(-/-) mice) has revealed its crucial role in the activation of the type I IFN response. The Bcl2l12 gene, encoding Bcl2L12 protein structurally related to the Bcl-2 family, was found to almost overlap with the Irf3 gene, and the null mutation previously introduced into the Irf3 allele resulted in the functional inactivation of the Bcl2l12 gene; therefore, the mice are correctly termed Irf3(-/-)Bcl2l12(-/-) mice. Embryonic fibroblasts from Irf3(-/-)Bcl2l12(-/-) mice (Irf3(-/-)Bcl2l12(-/-) MEFs) showed resistance to DNA damage-induced apoptosis, accompanied by impaired caspase cleavage. This apoptotic defect in Irf3(-/-)Bcl2l12(-/-) MEFs was rescued by the ectopic expression of Bcl2L12, but not IRF3. The Bcl2L12-mediated apoptotic response depended on the cell type and extracellular stimulus. In contrast, the previously reported defect in the induction of type I IFN genes by nucleic acids in Irf3(-/-)Bcl2l12(-/-) MEFs was rescued by expressing IRF3, but not Bcl2L12. Thus, our present study revealed, on the one hand, a cell type-dependent proapoptotic function of Bcl2L12 and, on the other hand, confirmed the essential role of IRF3 in type I IFN response. |
